Cell Reports r, r

throughput, sequencing-based, structure-mapping somal RNAs [rRNAs] and transfer RNAs [tRNAs]), and catalyticRecent findings have revealed unexpectedly pervasive tran-scription within animal genomes (Birney et al., 2007; Celniker brought our attention to a vast, evolutionarily conserved, post-transcriptional, regulatory network dependent on self or foreign double-stranded RNAs (dsRNAs) (Bartel, 2004; Carthew andet al., 2009), but only a very small proportion of these RNA transcripts are actually predicted to encode proteins. These Sontheimer, 2009). In animals, production of intra- and intermo-lecularly base-paired RNAs gives rise to 20–30 nt smRNAsapproach to identify the paired (double-stranded RNA [dsRNA]) and unpaired (single-stranded RNA [ssRNA]) components of the Drosophila mela-nogaster and Caenorhabditis elegans transcrip-tomes,which allows us to identify conserved features of RNA secondary structure in metazoans. From this analysis, we find that ssRNAs and dsRNAs are significantly correlated with specific epigenetic modifications. Additionally, we find key structural patterns across protein-coding transcripts that indicate that RNA folding demarcates regions of protein translation and likely affects microRNA-mediated regulation of mRNAs in animals. Finally, we identify and characterize 546 mRNAs whose folding pattern is significantly correlated between these metazoans, suggesting that their structure has some function. Overall, our findings provide a global assessment of RNA folding in animals